HO-1对糖尿病大鼠早期肾损伤的影响

基础医学与临床 ›› 2012, Vol. 32 ›› Issue (8): 911-915.

HO-1对糖尿病大鼠早期肾损伤的影响

裴华颖¹,邵杰敏²,赵小云²,邢邯英³,刘品力¹,张雨¹

1. 河北医科大学第二医院
2. 河北省人民医院
3. 河北省人民医院临床研究中心

收稿日期:2012-04-06 修回日期:2012-05-30 出版日期:2012-08-05 发布日期:2012-07-17
通讯作者: 裴华颖 E-mail:phuaying@gmail.com
基金资助:
河北省科技厅支撑计划项目;河北省卫生厅医学科学研究指令性课题

Effect of heme oxygenase-1 on diabetic rats with early stage of kidney injury

Received:2012-04-06 Revised:2012-05-30 Online:2012-08-05 Published:2012-07-17
Contact: Hua-Ying PEI E-mail:phuaying@gmail.com

摘要/Abstract

摘要： 目的探讨血红素加氧酶-1（HO-1）水平的变化对糖尿病肾损伤时肾脏内皮功能及肾损伤的影响。方法链脲佐菌素诱导糖尿病大鼠模型，分成4组:对照组、糖尿病（DM）组、Hemin (HO-1诱导剂) +DM组、ZnPP (HO-1抑制剂) +DM组。在5、10、15周时收集标本；IHC及RT-PCR法观察肾组织HO-1的表达，检测MDA含量、SOD活性、NO及iNOS、eNOS水平的变化。同时收集各组大鼠24h尿液测尿白蛋白排泄率（UAER）指标。结果与对照组比较，DM时大鼠肾脏局部MDA增加， HO-1的表达在5周时即增强，10周时有显著性差异（P<0.05）。在对照组肾组织中iNOS高于eNOS, DM时iNOS下降而eNOS明显升高；与DM5周组比较， Hemin+DM组HO-1表达明显增强（P<0.05），MDA含量下降，eNOS升高受抑制，UAER减少（P<0.05）；ZnPP+DM组HO-1表达减弱，MDA含量升高（P<0.01），eNOS增加，NO增加明显（P<0.05），UAER增加（P<0.05）。结论提高肾脏HO-1表达水平可减缓肾脏损伤。

关键词: 内皮功能, 血红素加氧酶-1, 糖尿病大鼠, 肾损伤

Abstract: Objective To explore the effect of heme oxygenase-1 (HO-1) on endothelial function and kidney injury in diabetic nephropathy. Methods Rats were divided into control, diabetes mellitus (DM) , Hemin (HO-1 inducer) and ZnPP (HO-1 inhibitor) groups. All samples were collected on 5w, 10w and 15w. Expression of HO-1 in renal tissue were examined by IHC and RT-PCR, malondialdehyde (MDA) contents, superoxide dismutase(SOD) activity, levels of NO product and iNOS，eNOS in renal tissue were detected. Urinary albumin excretion rate (UAER) was also observed. Results The content of MDA was progressively increased in kidney of DM rats. Up regulated HO-1 mRNA expression in renal tissue detected by RT-PCR and significantly enhanced of HO-1 expression detected by IHC from DM rats were observed when compared with those of control group. iNOS was decreased and eNOS was increased in DM rats. After pretreatment with Hemin for 5 weeks in DM rats, MDA and UAER were lower than that of DM 5w group. Alternatively, pretreatment with ZnPP in DM rats, a higher content of MDA, and UAER were measured. While eNOS was reduced after treatment with Hemin, NO product was obviously heightened following eNOS induced after administration Znpp. Conclusions Up regulation of HO-1 may ameliorate the renal injury in diabetic nephropathy.

Key words: endothelial function, Heme oxygenase-1, Diabetes mellitus rat, renal injury

裴华颖邵杰敏赵小云邢邯英刘品力张雨. HO-1对糖尿病大鼠早期肾损伤的影响[J]. 基础医学与临床, 2012, 32(8): 911-915.

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